A new strategy for enhancing S-Adenosyl-L-Methionine (SAMe) oral bioavailability: Preparation of SAMe loaded inulin nanoparticles for colon targeting with in vivo validation

S-Adenosylmethionine (SAMe) is a crucial endogenous molecule in vital biochemical processes such as DNA, RNA, and protein methylation. It has been found beneficial in the treatment of liver disease, osteoarthritis, and particularly depression. However, SAMe's therapeutic potential is limited by low bioavailability due to poor permeability and extensive liver metabolism. This study sought to improve SAMe's bioavailability by encapsulating it in inulin nanoparticles, utilizing a colon-targeted delivery system. Inulin, a prebiotic that promotes gut health by encouraging beneficial gut bacteria, is an ideal carrier for colon-specific drug delivery. Inulin nanoparticles were prepared using the desolvation method, incorporating sodium lauryl sulfate (SLS) for ion pairing with SAMe. The nanoparticles were spraycoated onto microcrystalline cellulose inert microspheres in a fluidized bed with Eudragit L30D-55 for colontargeted release (Nanoparticle-In-Microparticles, NIMs). Pharmacokinetic studies in rats showed that encapsulating SAMe in inulin nanoparticles resulted in a significant three-fold increase in bioavailability compared to its pure form. This enhancement highlights the potential of inulin nanoparticles as an effective delivery system for SAMe, particularly in colon-targeted therapies.